Murine experimental autoimmune thyroiditis is an animal model for human autoimmune thyroididtis (Graves and Hashimoto diseases). Thyroglobulin, (Tg) the major antigen in EAT, can, therefore, be used as an example of a tolerized self-antigen. It is the aim of this work to examine by limiting dilution precursor frequency analysis the number of lymphocytes reactive to mouse Tg present in a mouse. The studies will quantitate the number of precursor cell in specific, functional lymphocyte subsets which may be involved in pathogenesis, both in naive animals and during the progression of the induced disease. The genetic influences on the size of the Tg reactive lymphocyte pool will also be examined. The results from these experiments may possibly help to clarify the mechanism of tolerance to self-antigen. They will also allow for the first time to quantitatively define the changes in functional lymphocyte populations during the progression of an animal from the naive to autoimmune state. The methodology is well established. Precursor frequency analysis will be performed by limiting dilution. The T cell functions which will be studied and which may be the most informative are helper T cell activity, cell mediated lysis, Interleukin-2 production, and antigen specific proliferation.